During the initial four year funding period, the investigators have demonstrated the expression and significance of overexpression of EGF receptor in neoplasia of human glial tumors. This application is to study the expression profile of a number of cell cycle regulatory proteins in glial tumors with or without expression of mutated EGF receptor. The basis of this application is data generated by using a variety of brain tumor cell lines. Studies are proposed to: (1) Investigate biological properties of human glioblastoma cells that express the EGF receptor truncation mutants and relate these properties to the manner in which the mutants receptors affect cell cycle control; (2) Investigate the tumor and molecular biology associated with disruptions of the cell cycle checkpoint constituted by the p16, RB, cyclin D, CDK4, and CDK6 proteins; and (3) Investigate the tumor and molecular biology of the cell cycle checkpoint constituted by the p53, mdm2, and p21 glioma. Analysis of expression and biological effects of cell cycle proteins will contribute towards the development of a detailed and precise description of the fundamental mechanisms associated with glial tumor development and thereby advance information necessary to effectively treat individuals with glial tumors.